Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0006393
UniProt IDP28340
Primary gene name(s)POLD1
Synonym gene name(s)POLD
Protein nameDNA polymerase delta catalytic subunit
Protein functionAs the catalytic component of the trimeric, Pol-delta3 complex and tetrameric DNA polymerase delta complexes, Pol-delta4 complex, plays a crucial role in high fidelity genome replication, including in lagging strand synthesis, and repair. Exhibits both DNA polymerase and 3'- to 5'-exonuclease activities, PubMed:16510448, PubMed:19074196, PubMed:20334433, PubMed:24035200, PubMed:24022480. Requires the presence of accessory proteins POLD2, POLD3 and POLD4 for full activity. Depending upon the absence, Pol-delta3 or the presence of POLD4, Pol-delta4, displays differences in catalytic activity. Most notably, expresses higher proofreading activity in the context of Pol-delta3 compared with that of Pol-delta4, PubMed:19074196, PubMed:20334433. Although both Pol-delta3 and Pol-delta4 process Okazaki fragments in vitro, Pol-delta3 may be better suited to fulfill this task, exhibiting near-absence of strand displacement activity compared to Pol-delta4 and stalling on encounter with the 5'-blocking oligonucleotides. Pol-delta3 idling process may avoid the formation of a gap, while maintaining a nick that can be readily ligated, PubMed:24035200. Along with DNA polymerase kappa, DNA polymerase delta carries out approximately half of nucleotide excision repair, NER synthesis following UV irradiation, PubMed:20227374. Under conditions of DNA replication stress, in the presence of POLD3 and POLD4, may catalyze the repair of broken replication forks through break-induced replication, BIR, PubMed:24310611. Involved in the translesion synthesis, TLS of templates carrying O6-methylguanine or abasic sites, PubMed:19074196. {ECO:0000269|PubMed:16510448, ECO:0000269|PubMed:19074196, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:20334433, ECO:0000269|PubMed:24022480, ECO:0000269|PubMed:24035200, ECO:0000269|PubMed:24310611}.
Subcellular locationNucleus {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:22801543}. Note=Colocalizes with PCNA and POLD3 at S phase replication sites, PubMed:11595739. After UV irradiation, recruited to DNA damage sites within 2 hours, independently on the cell cycle phase, nor on PCNA ubiquitination. This recruitement requires POLD3, PCNA and RFC1-replication factor C complex, PubMed:20227374, PubMed:22801543. {ECO:0000269|PubMed:11595739, ECO:0000269|PubMed:20227374, ECO:0000269|PubMed:22801543}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: P28340
Gene Ontology
(Biological Process)
Complete annatation
base-excision repair, gap-filling [GO:0006287];
cellular response to UV [GO:0034644];
DNA damage response, detection of DNA damage [GO:0042769];
DNA repair [GO:0006281];
DNA replication [GO:0006260];
DNA replication proofreading [GO:0045004];
DNA strand elongation involved in DNA replication [GO:0006271];
DNA synthesis involved in DNA repair [GO:0000731];
fatty acid homeostasis [GO:0055089];
mismatch repair [GO:0006298];
nucleotide-excision repair, DNA gap filling [GO:0006297];
nucleotide-excision repair, DNA incision [GO:0033683];
nucleotide-excision repair, DNA incision, 5'-to lesion [GO:0006296];
response to UV [GO:0009411];
telomere maintenance [GO:0000723];
telomere maintenance via recombination [GO:0000722];
transcription-coupled nucleotide-excision repair [GO:0006283];
translesion synthesis [GO:0019985]
Gene Ontology
(Molecular Function)
Complete annatation
3'-5'-exodeoxyribonuclease activity [GO:0008296];
4 iron, 4 sulfur cluster binding [GO:0051539];
chromatin binding [GO:0003682];
damaged DNA binding [GO:0003684];
DNA binding [GO:0003677];
DNA-directed DNA polymerase activity [GO:0003887];
metal ion binding [GO:0046872];
nucleotide binding [GO:0000166]
Gene Ontology
(Cellular Component)
Complete annatation
aggresome [GO:0016235];
cytoplasm [GO:0005737];
delta DNA polymerase complex [GO:0043625];
membrane [GO:0016020];
nucleoplasm [GO:0005654];
nucleotide-excision repair complex [GO:0000109];
nucleus [GO:0005634]
Protein-protein interaction111420
Phylogenetic treeP28340
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
Brass et al., Science, 2008
Smith et al., J. Immunol, 2010
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model

DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.153077533276680.0006196681776948760.00239512579300727
AZA vs. DISU-0.02811644269896720.9123836217010120.994271142470137
AZA vs. IL70.3707555625809620.0572372767425040.693178115066193
AZA vs. SAHA0.1894494460406460.4400718067467840.787415175806649
DISU vs. CD3-1.194351992461140.001177916691972420.00477566331758804
DISU vs. IL70.3896444182585150.1235444175332570.460442064450042
DISU vs. SAHA0.2205225555406060.4555846203803490.795837010998848
DMSO vs. AZA0.04519800950252410.7900194096213341
DMSO vs. CD3-1.12075503926690.0005981503104933730.00218345879030353
DMSO vs. DISU0.07103527622251090.772293716383440.97150326349898
DMSO vs. IL70.3333066569313350.06650287917638610.49289883978905
DMSO vs. SAHA0.1394837356613950.5573301978733890.842226691487193
HIV vs. Mock in Activation0.1706835561549870.7845131509828830.999983755607037
HIV vs. Mock in Latency-0.1565552886356530.3526046040532320.999834320637052
IL7 vs. CD3-0.7765310210936240.01648041886267850.0449284415838583
SAHA vs. CD3-0.9865872182730180.006911311333005040.0187968709237297
SAHA vs. IL7-0.1834396728570930.4582895745096920.695135544994877
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change unknown
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) unknown
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.410166 0.00457947
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
1.003 0.96 0.918 0.798 0.91
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
-0.6 0.022 -0.47 0.1439 0.17 0.7827 DNA recombination; repair and maintenance (4hpi)
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

not found

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

not found

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa00230 Purine metabolism - Homo sapiens (human)
hsa00240 Pyrimidine metabolism - Homo sapiens (human)
hsa01100 Metabolic pathways - Homo sapiens (human)
hsa03030 DNA replication - Homo sapiens (human)
hsa03410 Base excision repair - Homo sapiens (human)
hsa03420 Nucleotide excision repair - Homo sapiens (human)
hsa03430 Mismatch repair - Homo sapiens (human)
hsa03440 Homologous recombination - Homo sapiens (human)
hsa05166 HTLV-I infection - Homo sapiens (human)